Administration of lymphocytes, tumor antigens, or tumor cells transduced with specific cytokine genes represent novel approaches for the treatment of cancer. By either providing antitumor effector cells or stimulating antitumor immunity at the tumor site these experimental modalities have resulted in decreased tumorigenicity and regression of existing tumors in a number of experimental models. In spite of these experimental results, the targeting of effector lymphocytes as well as anticancer cytokines and drug sensitivity factors to particular tumor sites has had limited clinical applications and shown limited clinical benefit, in part because of the complexities, in part because the preclinical models employed may have had limited predictive value. We have developed a valuable preclinical model in nude mice where to test novel cancer therapeutics. We considered the possibility that tumor cell killing might be induced by inoculation of the tumor-bearing host with benign cells which are normally destroyed if inoculated into the same host. We reasoned that by stimulating a local cytotoxic response in vivo one might achieve killing of tumor cells through a bystander effect. When injected subcutaneously into irradiated athymic (nude) mice, human B cells immortalized with Epstein-Barr virus (EBV) either fail to grow or give rise to small tumors that soon regress. The mechanism for this regression is not fully understood but has been attributed to residual host immunity. In the same experimental system, human Burkitt's lymphoma cells generally develop into lethal malignant tumors. We examined whether inoculation of EBV-immortalized B cells might have an antitumor effect against experimental Burkitt's lymphoma in athymic mice. Most of the established human Burkitt's tumors regressed after intratumor inoculations with EBV-immortalized B cells. In addition, a variety of other human malignant cell lines, representative of breast carcinoma,colon adenocarcinoma, sarcomas, myeloid leukemias, neuroblastoma, and other malignancies, regressed when tested in the same experimental nude mouse model. Thus, the experimental approach to Burkitt's lymphoma treatment described here exploits the ability of athymic mice to reject EBV-immortalized B cells to target an effective antitumor response to malignant cells normally incapable of eliciting it. Recently, we have began to study the mechanisms mediating tumor regression in this experimental system, and found that the interferon-inducible chemokine IP-10 contributes to tumor regression. Tosato, G, Sgadari C., Taga K., Pike S., Rosenberg, A., Magrath IT, and K. Bhatia. Treatment of experimental Burkitt's lymphoma with normal human B cells immortalized with EBV Blood 83:776-784, 1994. Angiolillo A., Sgadari C., Reaman G., and Tosato G., Regression of Experimental human leukemias and solid tumors induced by EBV-immortalized cells. Leukemia and Lymphoma